Disease relevance of pyrazinoate

• Susceptible strains of tubercle bacilli convert PZA to pyrazinoic acid (POA) through pyrazinamidase (PZase), which resistant strains and Mycobacterium bovis bacille Calmette-Guérin lack [1].
• Complicating arthralgias occur due to hyperuricaemia induced by the inhibition of renal tubular secretion of uric acid by pyrazinoic acid, the main PZA metabolite [2].
• Nitrilase-catalyzed production of pyrazinoic acid, an antimycobacterial agent, from cyanopyrazine by resting cells of Rhodococcus rhodochrous J1 [3].
• Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure [4].

High impact information on pyrazinoate

• Finally, in the presence of an inward Na+ gradient, low doses of pyrazinoate or nicotinate stimulated urate uptake, and higher doses of pyrazinoate or nicotinate inhibited urate accumulation, thereby mimicking in vitro the paradoxical effects of drugs on renal urate excretion that have been observed in vivo [5].
• PZA is a prodrug that has to be converted to the active form pyrazinoic acid by pyrazinamidase (PZase) activity, encoded by the pncA gene of Mycobacterium tuberculosis, and loss of PZase activity is associated with PZA resistance [6].
• Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug that requires conversion to the bactericidal compound pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) activity of nicotinamidase to show activity against Mycobacterium tuberculosis [7].
• Quantitative structure-activity relationships for the in vitro antimycobacterial activity of pyrazinoic acid esters [8].
• Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium tuberculosis: investigations into mechanism of action of and mechanism of resistance to pyrazinamide [9].

Chemical compound and disease context of pyrazinoate

• Does pyrazinoic acid as an active moiety of pyrazinamide have specific activity against Mycobacterium tuberculosis [10]?

Biological context of pyrazinoate

• Diuresis and saluresis produced by MK-196 are not influenced by pyrazinoate [11].
• The PZase activity was measured by pyrazinamide deamination to pyrazinoic acid and ammonia, and the entire pncA sequence including the 410 bp upstream from the start codon was determined by DNA sequencing of purified PCR products [12].
• To investigate whether this natural resistance to PZA is due to inability of the M. avium PZase to convert PZA to bactericidal POA, the M. avium PZase gene (pncA) was cloned by using the M. tuberculosis pncA gene as a probe [13].
• Pharmacokinetics of pyrazinoyl-guanidine, 3-aminopyrazinoyl-guanidine and their corresponding pyrazinoic acid metabolites in humans and dogs [14].
• These metabolic effects were also investigated after: (a) pyrazinoic acid (PZA), a metabolite of PZG; (b) 3-amino-PZG, an analog of PZG, and (c) 3-amino-PZA, a hydrolytic product of 3-amino-PZG [15].

Anatomical context of pyrazinoate

• Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system [1].
• Change in the transport of uric acid under the influence of pyrazinoic acid: in vitro studies with human and rabbit peritoneum [16].
• Methods for the estimation of pyrazinamide and pyrazinoic acid in body fluids [17].

Associations of pyrazinoate with other chemical compounds

• Further studies to assess the effects of modifications of the alcohol and pyrazine moieties of pyrazinoate esters on in vitro and in vivo antituberculosis activity are under way [9].
• Effects of p-aminohippurate and pyrazinoate on urate excretion in Cebus monkeys [18].
• Effects of p-aminohippurate and pyrazinoate on the renal excretion of salicylate in the rat: a micropuncture study [19].
• Compared to a pH equilibrium condition (pHin = 7.4; pHout = 7.4), an outwardly directed OH- gradient (pHin = 7.4; pHout = 5.8) stimulated markedly both lactate and pyrazinoate uptake with overshoots exceeding 2 times that of the steady state [20].
• Pyrazinoylguanidine (PZG), 3-aminopyrazinoylguanidine (NH2PZG) and their pyrazinoic acid metabolites were measured by a new reverse-phase HPLC method in the serum of dogs and humans after administration of PZG, NH2PZG or 2-pyrazinoic acid (PZA) [14].

Gene context of pyrazinoate

• Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide [21].
• Analysis of fatty acid synthesis in crude mycobacterial cell extracts demonstrated that pyrazinoic acid failed to directly modulate the fatty acid synthase activity catalyzed by fatty acid synthase I (FAS-I) [22].
• Two substrates, oxonate (a competitive uricase inhibitor) and pyrazinoate, that inhibit renal electrogenic urate transport also block UAT activity [23].
• Urate precession and recovery did not change after addition of PAH (1.5-6.4 mm) to [14C]urate-[3H]inulin solutions, whereas they decreased significantly in the experimental kidney after pyrazinoate (1.6-3.2 mM) addition [24].
• Growth-promoting activity of pyrazinoic acid, a putative active compound of antituberculosis drug pyrazinamide, in niacin-deficient rats through the inhibition of ACMSD activity [25].

Analytical, diagnostic and therapeutic context of pyrazinoate

• The area under the curve of pyrazinoic acid (the main metabolite) is increased from 97 to 280 mg.h.l-1 with a half-life twice as much as that of the control group [26].
• The intraperitoneal or oral administration of pyrazinamide and pyrazinoic acid (pyrazine 2-carboxylic acid) resulted in a marked increase of the NAD content in rat liver [27].

References